Patients and Methods: Patients (P) with untreated HER2-negative BC were eligible if they had cT3/4a-d; or estrogen (ER) and progesterone (PgR) receptor-negative; or ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1) disease, and no increased cardiac or bleeding risks. P were randomized to receive 4 cycles epirubicin/cyclophosphamide (EC) (90/600 mg/m2) q3w followed by 4 cycles docetaxel (D) (100mg/m2) with or without concomitant Bev 15mg/kg q3w added to chemotherapy cycles. P not clinically responding to EC ± Bev were considered as treatment failures and entered another part of the protocol. pCR was defined as no invasive or non-invasive tumor residuals in breast and nodes. We assumed a pCR rate of 14% (based on GeparDuo) and expected a pCR of 18.9% for EC-D+Bev (odds ratio 1.43). A two-sided Pearson's Chi2 with α=0.05 and β=0.20 calculated a sample size of 1934 P.

Results: Between 05/07 and 06/10 1889 P were randomized to EC-D (N=944) and EC-D+Bev (N=945). Median tumor size was 40/40 [-Bev/+Bev] mm (clinically) and 29/29 mm (sonographically); 6.3%/5.8% had T4a-c, 6.6%/6.7% T4d, 2.0%/2.1% bilateral, 14.3%/13.8% multifocal, and 8.8%/10.0% multicentric disease, 89.3%/88.9% had non-lobular, 42.5%/43.3% grade 3, 57.1%/58.4% node-positive, and 34.5%/33.6% ER and PgR-negative (triple-negative) disease. So far, 24% and 17% of patients did not respond to the first 4 cycles of EC-Bev and EC+Bev, respectively, and discontinued randomized treatment. The last randomized P will have surgery early Dec'10. Results on histological response and surgical outcome will be reported.

Conclusion: The GeparQuinto trial will provide for the first time randomized phase III efficacy data on Bev in combination to chemotherapy for patients with early breast cancer. pCR after Bev treatment can be considered as a surrogate marker for long term outcome but this has to be examined during further follow up of the patients.